It is proposed to continue studies on the biologic properties of the Epstein-Barr virus (EBV) and the immune responses it evokes in infectious mononucleosis (IM), Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC) and in viral carriers under the influence of immunosuppressive diseases or therapy. The plans include search for more potent sources of EBV and cells more susceptible to the virus than now available; efforts to differentiate additional EBV-related antigen-antibody systems by immunofluorescence and immunoelectron microscopy; improvement of procedures for detection of EBV-associated nuclear antigen (EBNA) and application of the procedures to a search for EBV-transformed cells among lymphocyte populations of IM patients and viral carriers, in biopsies of carcinomas of head and neck as an aid in the diagnosis of NPC, in EBV-exposed cord blood lymphocyte cultures as a rapid, quantitative assay of transformation, and to titration of antibodies to EBNA in sera from various types of patients and correlation of anti-EBNA and other EBV-related antibody titers to clinical status and evidence of immunologic defects or antigen-antibody complexes. The main thrust will be directed toward development of methods for detection of immune responses to EBV-transformed cells, whether humoral, cell-mediated or a combination of both. These studies entail evaluation of techniques for measuring anti-cellular immune reactions and their adaptation to the specific purpose, search for most suitable target cells, and selection of lymphocyte populations which contain, without or after antigenic stimulation, EBV-specific effector cells active per se or in presence of sera from various catergories of donors. Once dependable test systems have evolved, they will be used for detection of blocking factors in sera from patients in advanced stages of BL and NPC with sera from patients in prolonged remissions serving as controls. These efforts might afford explanations for self limitation of lymphoproliferation in IM and unrestrained growth of EBNA positive cells in BL and NPC patients and, in turn, provide further evidence for an etiologic association of EBV with these two malignancies.